Tag: risk factors

Covid-19: Antibody “signature” could predict risk of long covid

Researchers have identified an immunoglobulin “signature” that could be used to predict which patients are most at risk of developing post-acute covid syndrome (PACS), otherwise known as long covid.

In a multicentre prospective study, 175 patients with covid-19 and 40 healthy control group participants were followed for up to a year. More than half of the patients with covid reported long covid symptoms lasting longer than a month. Those who developed long covid were found to have lower levels of IgM and IgG3 antibodies than those who quickly recovered, found the research, published in Nature Communications.1 A history of asthma was also highly associated with PACS, the study found.

The researchers combined data on immunoglobulin concentrations with a patient’s age, history of asthma, and five symptoms during the primary infection to develop a PACS score that could predict the risk of developing long term illness. The PACS score was then validated in an independent group of 395 people with covid-19.

The researchers, from the University of Zurich, said that the score might be especially helpful in hospital settings for early identification of those patients at a very high risk of developing PACS. It could also allow the study of targeted preventive treatments such as inhaled corticosteroids or intravenous immunoglobulin treatments.

The researchers said more research was still needed but that a PACS score or long covid risk calculator would be available soon at pacs-score.com.

The study’s limitations included that participants were infected between April 2020 and August 2021, before the omicron variant took hold. And the study didn’t take into account participants’ vaccination status.

Claire Steves, a senior clinical lecturer at King’s College London, welcomed the research, saying, “With cases high still, more people are at risk of developing long term symptoms. We urgently need to scale up research on how to prevent this happening. Tools such as these predictive models could be used to identify people at higher risk for enrolment into research trials for therapeutics.”

But she added, “This is a small study that was undertaken in a selected population, and so in particular the immune findings do need to be replicated elsewhere.”

Amitava Banerjee, professor of clinical data science and honorary consultant cardiologist at University College London, commented, “There are three implications from this research. First, the immunoglobulin signature points more clearly towards the mechanism of disease, although replication of the results in different, larger cohorts is needed. Second, this raises the possibility of being able to predict the risk of long covid in individuals post-initial infection. Third, further research is required to understand whether similar risk factor profiles can be used to predict the prognosis or speed of recovery.”

Read the rest of this article HERE.

Source: Jacqui Wise. Covid-19: Antibody “signature” could predict risk of long covid. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o245 (Published 28 January 2022)

Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort

Abstract:

Background: The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed.

Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results: Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions: Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Source: Strahm C, Seneghini M, Güsewell S, Egger T, Leal O, Brucher A, Lemmenmeier E, Meier Kleeb D, Möller JC, Rieder P, Ruetti M, Rutz R, Schmid HR, Stocker R, Vuichard-Gysin D, Wiggli B, Besold U, Kuster SP, McGeer A, Risch L, Friedl A, Schlegel M, Schmid D, Vernazza P, Kahlert CR, Kohler P. Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort. Clin Infect Dis. 2022 Jan 28:ciac054. doi: 10.1093/cid/ciac054. Epub ahead of print. PMID: 35090015. https://pubmed.ncbi.nlm.nih.gov/35090015/  (Full text available as PDF file)

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome

Abstract:

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which – combined with age, history of asthma bronchiale, and five symptoms during primary infection – is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

Source: Cervia C, Zurbuchen Y, Taeschler P, Ballouz T, Menges D, Hasler S, Adamo S, Raeber ME, Bächli E, Rudiger A, Stüssi-Helbling M, Huber LC, Nilsson J, Held U, Puhan MA, Boyman O. Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome. Nat Commun. 2022 Jan 25;13(1):446. doi: 10.1038/s41467-021-27797-1. PMID: 35078982. https://www.nature.com/articles/s41467-021-27797-1 (Full text)

Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed.
Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males.
After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671–3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040–2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081–1.886, exertion: adj OR 1.409, 95%CI 1.109–1.791), pain (adj OR 1.349, 95%CI 1.059–1.720), hair loss (adj OR 4.529, 95%CI 2.784–7.368), ocular problems (adj OR 1.981, 95%CI 1.185–3.312), depressive levels (adj OR 1.606, 95%CI 1.002–2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097–2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers.
Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Pellicer-Valero ÓJ, Navarro-Pardo E, Gómez-Mayordomo V, Cuadrado ML, Arias-Navalón JA, Cigarán-Méndez M, Hernández-Barrera V, Arendt-Nielsen L. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J Clin Med. 2022 Jan 14;11(2):413. doi: 10.3390/jcm11020413. PMID: 35054108; PMCID: PMC8778106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778106/ (Full text)
Source:

Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

Summary:

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms.
We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Source: : Su, Y., Yuan, D., Chen, D.G., Ng, R.H., Wang, K., Choi, J., Li, S., Hong, S., Zhang, R., Xie, J., Kornilov, S.A., Scherler, K., Pavlovitch-Bedzyk, A.J., Dong, S., Lausted, C., Lee, I., Fallen, S., Dai, C.L., Baloni, P., Smith, B., Duvvuri, V.R., Anderson, K.G., Li, J., Yang, F., Duncombe, C.J., McCulloch, D.J., Rostomily, C., Troisch, P., Zhou, J., Mackay, S., DeGottardi, Q., May, D.H, Taniguchi, R., Gittelman, R.M, Klinger, M., Snyder, T.M, Roper, R., Wojciechowska, G., Murray, K., Edmark, R., Evans, S., Jones, L., Zhou, Y., Rowen, L., Liu, R., Chour, W., Algren, H.A, Berrington, W.R., Wallick, J.A., Cochran, R.A., Micikas, M.E., the ISB-Swedish COVID19 Biobanking Unit, Terri Wrin, Petropoulos, C.J., Cole, H.R., Fischer, T.D., Wei, W., Hoon, D.S.B., Price, N.D., Subramanian, N., Hill, J.A, Hadlock, J., Magis, A.T., Ribas, A., Lanier, L.L., Boyd, S.D., Bluestone, J.A., Chu, H., Hood, L., Gottardo, R., Greenberg, P.D., Davis, M.M., Goldman, J.D., Heath, J.R., Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae, Cell (2022), doi: https://doi.org/10.1016/j.cell.2022.01.014. (Full text)

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Abstract:

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed.

We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients.

Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

Source: König RS, Albrich WC, Kahlert CR, Bahr LS, Löber U, Vernazza P, Scheibenbogen C, Forslund SK. The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Front Immunol. 2022 Jan 3;12:628741. doi: 10.3389/fimmu.2021.628741. PMID: 35046929; PMCID: PMC8761622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761622/ (Full text)

 

Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

Objective: This multicenter study investigated clinical risk factors associated with the number of long-term post-COVID symptoms.

Methods: Clinical features, symptoms at hospital admission, hospitalization data, and the number of post-COVID symptoms was systematically assessed from patients recovered from COVID-19 at four hospitals in Madrid (Spain) from February 20 to May 31, 2020.

Results: Overall, 1,969 patients (46.5% women, age: 61, SD: 16 years) were randomly assessed at 8.4 months (SD 1.5) after hospital discharge. Female gender (OR1.82, 95%CI 1.57-2.10), number of morbidities (OR1.182, 95%CI 1.08-1.29), number of symptoms at hospital admission (OR1.309, 95%CI 1.15-1.49) and days at the hospital (OR1.01, 95%CI 1.007-1.017) were associated (all, P<0.001) with more long-term post-COVID symptoms. Further, vomiting (OR1.78, 95%CI 1.26-2.52), throat pain (OR1.36, 95%CI 1.02-1.81), diarrhoea (OR1.51, 95%CI 1.25-1.82), dyspnea (OR1.20, 95%CI 1.01-1.41), or headache (OR1.50, 95%CI 1.28-1.75) as symptoms at hospital admission were also associated (all, P<0.01) with a higher number of post-COVID symptoms.

Conclusion: This multicenter study found that a higher number of symptoms at hospital admission was the most relevant risk factor for developing more post-COVID symptoms, supporting the assumption that a higher symptom load at the acute phase is associated with a greater likelihood of long-term post-COVID symptoms.

Source: Fernández-de-Las-Peñas C, Pellicer-Valero OJ, Navarro-Pardo E, Palacios-Ceña D, Florencio LL, Guijarro C, Martín-Guerrero JD. Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study. Int J Infect Dis. 2022 Jan 8:S1201-9712(22)00007-8. doi: 10.1016/j.ijid.2022.01.007. Epub ahead of print. PMID: 35017102; PMCID: PMC8743274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743274/ (Full text)

Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment

Abstract:

Background: Cognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection.

Aims: In this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19).

Methods: One hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA).

Results: Abnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1-2, 2020) (OR 1.27; 95% CI 1.05-1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1-2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53-14.63; p = 0.003) during the acute phase of the disease.

Discussion: This longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease.

Conclusions: These findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up.

Source: Cristillo V, Pilotto A, Cotti Piccinelli S, Bonzi G, Canale A, Gipponi S, Bezzi M, Leonardi M, Padovani A; Neuro Covid Next Study group. Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment. Aging Clin Exp Res. 2022 Jan 11:1–4. doi: 10.1007/s40520-021-02042-3. Epub ahead of print. PMID: 35014002; PMCID: PMC8747881. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747881/ (Full text)

The Long-COVID Syndrome: smoking and enhanced suicide risk

Extract:

The QJM has been at the forefront in highlighting the mental health problems associated with COVID-19 infection in society.1–6 In a Commentary piece in this issue of the Journal, Leo Sher, Professor of Psychiatry from the Mount Sinai School of Medicine, highlights the role of smoking being associated with a worse prognosis in acute infections and enhancing the risk of suicide in patients suffering persistent disabling symptoms associated with the Long-COVID Syndrome.

It is well recognized that smoking is associated with suicidal ideation, suicide attempts, suicide death and a contributing factor in the pathophysiology of suicide. The author highlights the evidence that suggests that the COVID-19 pandemic has led to increased tobacco consumption as smokers use more tobacco to cope with pandemic-related stress, anxiety, depression and loneliness. Smoking will have significant psychobiological effects resulting in enhanced impulsivity and aggression which will be compounded by in particular the brain-related symptoms…

Source: Seamas C Donnelly, The Long-COVID Syndrome: smoking and enhanced suicide risk, QJM: An International Journal of Medicine, Volume 114, Issue 11, November 2021, Page 765, https://doi.org/10.1093/qjmed/hcab300

Physical, cognitive and mental health impacts of COVID-19 following hospitalisation – a multi-centre prospective cohort study

Abstract:

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood.

Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function.

Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity.

Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services.

Source: Sigfrid, Louise, et al. “Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.” medRxiv (2021).  https://www.medrxiv.org/content/10.1101/2021.03.22.21254057v1.full-text (Full text)